Immune response (Ir) genes, which control an animal's ability to respond immunologically to specific antigenic determinants, map in the genome within the major histocompatibility complex. The overall objective of this project is to investigate the role of the cell surface histocompatibility antigens in the development of specific immune responses. Toward that end, we have been studying the effects of antibodies directed at histocompatibility region antigens on cell-mediated immune responses. Our studies in guinea pigs have demonstrated that anti-histocompatibility sera specifically suppress those immune responses controlled by Ir genes linked to the genes controlling the expression of the target histocompatibility antigen. Suppression does not appear to result from a block of antigen/lymphocyte interaction; but, rather, from an antibody-induced alteration of the lymphocyte membrane that renders the cell unresponsive to the antigenic signal to proliferate. Most of the studies in this area have involved suppression of antigen-stimulated DNA synthesis. Our recent studies have shown that antigen-stimulated RNA and protein synthesis are suppressed in a like manner. Current studies are directed at earlier events following antigen stimulation, to identify which biochemical events that follow the interaction of antigen with its lymphocyte receptor are blocked by antibody to histocompatibility antigens. BIBLIOGRAPHIC REFERENCES: Bluestein, H. G. and Zvaifler, N. J. Brain reactive lymphocytotoxic antibodies in the serum of patients with systemic lupus erythematosus. J. Clin. Invest. 57:509, 1976. Zvaifler, N. J. and Bluestein, H. G. Lymphocytotoxic activity in the cryoprecipitates from serum of patients with SLE. Arthritis Rheum. 19:844, 1976.